Moderate alcohol consumption is associated with increased radiological progression in women, but not in men, with early rheumatoid arthritis: results from the ESPOIR cohort (Étude et Suivi des Polyarthrites Indifférenciées Récentes).

OBJECTIVE: We conducted this study to determine whether alcohol consumption influences radiological progression in early rheumatoid arthritis (RA). METHOD: Patients fulfilling the European League Against Rheumatism/American College of Rheumatology 2010 criteria in the early arthritis cohort ESPOIR (Étude et Suivi des Polyarthrites Indifférenciées Récentes) were included in this study. Alcohol consumption was collected at baseline and at each visit. We classified alcohol consumption into three groups: abstinent (0 g/day), moderate (≤ 20 g/day for women, ≤ 30 g/day for men), and abuse (> 20 g/day for women, > 30 g/day for men). The primary outcome was the occurrence of radiological progression, defined as an increase ≥ 5 points in the total Sharp/van der Heijde score. We investigated whether alcohol consumption is predictive of radiological progression at 1, 3, and 5 years by univariate and multivariate analysis adjusted for age, baseline erosion, rheumatoid factor, anti-citrullinated peptide antibody, smoking status, body mass index, and treatment with leflunomide or methotrexate and biologics. RESULTS: The study included 596 patients. When considering the influence of gender on the interaction between alcohol consumption and radiological progression, we showed a deleterious effect of moderate consumption in women [odds ratio (OR) = 1.73, 95% confidence interval (CI) 1.01; 2.96, p = 0.045] and a trend towards a protective effect of moderate consumption in men (OR = 0.50, 95% CI 0.21; 1.16, p = 0.106) in multivariate analysis. CONCLUSION: Our data suggest a deleterious effect of moderate consumption of alcohol on radiological progression in women, but not in men, with early RA.

Challenges of cardiovascular risk assessment in the routine rheumatology outpatient setting: an observational study of 110 rheumatoid arthritis patients.

OBJECTIVE: An annual assessment of cardiovascular (CV) risk factors in rheumatoid arthritis (RA) is recommended, but its practical modalities have not been determined. The objective was to assess the feasibility and usefulness of a standardized CV risk assessment in RA, performed by rheumatologists during outpatient clinics. METHODS: We used a cross-sectional design within a network of rheumatologists. Each rheumatologist included 5 consecutive unselected patients with definite RA. Data collection included standardized assessment of CV risk factors: blood pressure, interpretation of glycemia and of lipid levels, and calculation of the Framingham CV risk score. Outcome criteria included feasibility (missing data and time taken to assess the patients) and usefulness (the CV risk assessment was considered useful if at least 1 modifiable and previously unknown CV risk factor was evidenced). RESULTS: Twenty-two rheumatologists (77% in office-based practice) assessed 110 RA patients. The mean ± SD age was 57 ± 10 years, and the mean ± SD RA duration was 11 ± 9 years; 50 patients (45%) were treated with biologic agents, and 76% were women. Regarding feasibility, missing data were most frequent for glycemia (27% of patients) and cholesterolemia (14% of patients). The mean ± SD duration of the CV risk assessment was 15 ± 5 minutes. The CV risk assessment was considered useful in 33 patients (30%), evidencing dyslipidemia (15% of patients) or high blood pressure (9% of patients) as the most frequently previously unknown CV risk factor. CONCLUSION: The assessment of CV risk factors is feasible, but labor intensive, during an outpatient rheumatology clinic. This assessment identified modifiable CV risk factors in 30% of the patients. These results suggest that RA patients are not sufficiently assessed and treated for CV risk factors.

Factors associated with severe skin infections in patients treated with biologic therapies for inflammatory rheumatic diseases.

BACKGROUND: The incidence of severe infections is increased under biologic therapies and the skin is the second localization. OBJECTIVE: To appraise the factors associated with severe skin infections (SSI) in patients under biologic therapies for inflammatory rheumatic diseases (IRD). METHODS: We performed a case-control (ratio 1:3) study nested in a prospective cohort of patients with IRD. SSI was defined as requiring hospitalization or intravenous anti-infectious therapy. We defined two imbedded periods: period A was the time window between the first biologic therapy and the SSI; period B was the last 3 or 12 months (for tumor necrosis factor blockers or rituximab, respectively) before the SSI. RESULTS: Among 4,361 patients with IRD, 29 had a SSI under biologic therapy. In multivariate analyses, SSI were significantly associated with smoking, baseline C-reactive protein and gammaglobulinemia, non-steroidal anti-inflammatory drugs before biologic therapy, cumulative dose of steroids, concomitant steroids during period A, number of different biologic therapies during period A, treatment with infliximab during period A, period B or as first biologic therapy and treatment at high dose during period B. CONCLUSION: In patients under biologic therapies for IRD, the risk of SSI is associated with several factors including tobacco, treatment with infliximab or high dose range.

Risk of serious infections during rituximab, abatacept and anakinra treatments for rheumatoid arthritis: meta-analyses of randomised placebo-controlled trials.

BACKGROUND: Tumour necrosis factor alpha blockers in rheumatoid arthritis are known to increase the risk of serious infections defined as life-threatening, requiring hospitalisation or intravenous antibiotics. Recently, new biological agents have become available. Their safety is an important issue. PURPOSE: To assess if biological agents, ie rituximab, abatacept and anakinra increase the risk of serious infections in patients with rheumatoid arthritis in published randomised controlled trials. DATA SOURCE: A systematic review of the literature using PUBMED, EMBASE, Cochrane library and abstracts databases (American College of Rheumatology and European League Against Rheumatism annual meetings) was performed up to October 2007. This search was completed with data from the Food and Drug Administration, the European Agency for the Evaluation of Medicinal Products and manufacturers. DATA EXTRACTION: Three fixed-effect meta-analyses were performed to compare serious infection rates between each biological agent and placebo. Pooled odds ratios (ORs) were calculated, using the Mantel-Haenszel method with a continuity correction. DATA SYNTHESIS: Twelve randomised controlled trials with data concerning serious infections were analysed (three for rituximab, five for abatacept and four for anakinra). They included 745 patients, 1960 patients, 2062 patients and 2112 patients treated by rituximab, abatacept, anakinra and placebo respectively. The overall pooled ORs did not reveal a statistically significant increased risk of serious infection for abatacept and rituximab; this risk was increased for high doses of anakinra (> or =100 mg daily) versus low dose and placebo (ORs = 9.63 (95% CI, 1.31 to 70.91) and 3.40 (95% CI, 1.11 to 10.46) respectively). CONCLUSIONS: These meta-analyses did not reveal a significant increase in the risk of serious infections during rituximab or abatacept treatments in patients with rheumatoid arthritis; however, high doses of anakinra may increase this risk, especially when patients have comorbidity factors. Large studies must be performed to confirm this safety profile in daily practice.

Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research.

OBJECTIVE: To perform a systematic literature review of the long-term safety of methotrexate (MTX) monotherapy in rheumatoid arthritis (RA). METHODS: A search was performed in Medline, Cochrane and EMBASE. Adults with RA who had received MTX monotherapy for more than 2 years were studied. RESULTS: 88 published studies were included. Over 12 years of treatment, the termination rate of MTX due to toxicity was less than for sulfasalazine, gold, d-penicillamine and higher than for hydroxychloroquine (level of evidence 2a-2b). Long-term use of MTX does not appear to be a risk factor for serious infections, including herpes zoster (2b-4), and could provide a survival benefit by reducing cardiovascular mortality (2b). The prevalence of raised liver enzymes (more than twice the upper limit of normal) is close to 13% of patients; 3.7% of patients stopped MTX permanently owing to liver toxicity (2b). Data on the risk for liver fibrosis/cirrhosis are conflicting: a meta-analysis showed an incidence of fibrosis of 2.7% after 4 years of MTX (2a). However, two other studies on sequential liver biopsies did not show evidence for developing severe damage (2b). Insufficient data are available to fully assess the risk of lymphoma and malignancies, although there is no strong evidence of increased risk (2b-4). CONCLUSION: This systematic literature search on MTX monotherapy with relatively low-dose use during at least 2 years shows favourable long-term safety.

Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative.

OBJECTIVES: To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders. METHODS: 751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007-8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005-7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases. CONCLUSIONS: Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use.

Complication rates of 127 surgical procedures performed in rheumatic patients receiving tumor necrosis factor alpha blockers.

OBJECTIVE: Tumor necrosis factor (TNF) blockers have been reported to increase the risk of infections, thrombosis, and delayed healing. However, there is little data on the risk of complications after surgery in rheumatic patients receiving TNF blockers. The aim of this study was to assess the complication rate after surgery in such patients, to assess the effect of interrupting TNF blocker therapy, and to identify other potential predictors of complications. METHODS: This was a systematic, retrospective monocenter study of all patients treated with TNF blockers and who underwent surgery. Complications were recorded and complication rates were compared based on the type of surgery and the timing of the discontinuation of TNF blockers before surgery (above 2 or 5 half-lives). The complication rates were compared with those reported in the literature (orthopaedic procedures in RA patients: 7%, abdominal surgery: 13%). RESULTS: Between 1997 and 2004, 770 patients were treated with TNF blockers of whom 92 underwent surgery (127 surgical procedures). The most frequent underlying disease was rheumatoid arthritis (77%). Most of the surgical procedures were orthopaedic (85%). The complication rates for orthopaedic procedures and for abdominal procedures were 13% and 43%, respectively. The infection rate after orthopaedic procedures was 6.5%. Interrupting therapy before surgery did not significantly decrease the postoperative complication risk. There were no independent factors predicting complications. CONCLUSION: In daily practice the complication rate after surgery is high in patients treated with TNF blockers. Discontinuing TNF therapy before surgery should be considered, although this study did not clearly demonstrate its role.

Infections during tumour necrosis factor-alpha blocker therapy for rheumatic diseases in daily practice: a systematic retrospective study of 709 patients.

OBJECTIVE: To evaluate the rate of infections in rheumatic patients treated with tumour necrosis factor (TNF)-alpha blockers in daily practice and to determine potential risk factors of infections. METHODS: Systematic retrospective study was conducted in a tertiary-referral centre of all patients receiving at least one TNF-alpha blocker, between 1997 and December 2004. Serious infections were defined as life-threatening, requiring hospitalization or sequelae. The incidence of infections during the first TNF-alpha blocker course was compared with the incidence during the period just before such therapy, in the same patients and a number needed to harm was calculated. Univariate and multivariate analysis between patients who suffered from at least one infection during treatment or not, was conducted in order to determine potential associated risk factors. RESULTS: Among the 709 patients treated with at least one TNF-alpha blocker, 57.7% had rheumatoid arthritis; a total of 275 infectious events in 245 patients (34.5%) were reported during all treatment courses. Among these infections, 47 infections in 44 patients (6.2%) fulfilled the definition of serious infections. The incidence rate of serious infections was 3.4 +/- 38.7 per 100 patient-yrs before TNF-alpha blocker therapy vs 10.5 +/- 86.9 during the first TNF-alpha blocker course (P = 0.03, number needed to harm = 14). The single risk factor picked up by multivariate analysis to explain infections was previous joint surgery [odds ratio (OR) = 2.07, 95% confidence interval (CI) = (1.43-2.98), P < 0.0001] and, if surgery was taken out of the model, the cumulative dose of steroids [OR = 1.28 (1.04-1.59), P = 0.02]. CONCLUSION: The rate of serious infections during TNF-alpha blocker treatment observed in daily practice conditions was much higher than in phase III trials evaluating TNF-alpha blockers. Serious infections are frequent in daily practice and close monitoring is required.

Efficacy of tumour necrosis factor blockers in reducing uveitis flares in patients with spondylarthropathy: a retrospective study.

OBJECTIVE: To evaluate the efficacy of anti-tumour necrosis factor (TNF) treatments (given for rheumatological manifestations) in reducing uveitis flares in patients with spondylarthropathy in daily practice. METHODS: A retrospective observational study of all patients with spondylarthropathy with at least one uveitis flare treated with anti-TNF in one centre (December 1997-December 2004). The number of uveitis flares per 100 patient-years was compared before and during anti-TNF treatment; each patient was his or her own control. The relative risk (RR) and the number needed to treat (NNT) were calculated. RESULTS: 46 patients with spondylarthropathy treated with anti-TNF drugs had at least one uveitis flare (33 treated with anti-TNF antibodies, infliximab or adalimumab, and 13 with soluble TNF receptor, etanercept). The mean age at first symptoms was 26 years, 71% were men. Patients were followed for 15.2 years (mean) before anti-TNF versus 1.2 years during anti-TNF treatment. The number of uveitis flares per 100 patient-years before and during anti-TNF were, respectively: for all anti-TNF treatments,-51.8 v 21.4 (p = 0.03), RR = 2.4, NNT = 3 (95% confidence interval (CI) 2 to 5); for soluble TNF receptor-54.6 v 58.5 (p = 0.92), RR = 0.9; and for anti-TNF antibodies-50.6 v 6.8 (p = 0.001), RR = 7.4, NNT = 2 (95% CI 2 to 5). CONCLUSION: Anti-TNF treatments were efficacious in decreasing the number of uveitis flares in patients with spondylarthropathy. Anti-TNF antibodies decreased the rate of uveitis flares, whereas soluble TNF receptor did not seem to decrease this rate. These results could have consequences for the choice of anti-TNF treatment in certain patients.